Benzalkonium chloride (BAC) and chlorhexidine digluconate (CDG) were applied to rabbit and cat corneal epithelium in clinically used concentrations. Corneas were fixed 1/2 hr later and examined by scanning electron microscopy (SEM). BAC was found to produce a progressive increase in damage at concentrations between 0.001% and 0.01% as determined by SEM. CGD produced less damage than BAC at any concentration. Cats lacrimated copiously and blinked frequently after instillation of drops; rabbits did not. No significant difference was found between the two species, however, in their response to the preservative agents tested. It is presumed that binding of these surface active agents occurs almost immediately and is unaffected by tear film dilution. Studies measuring permeability increase in the human eye after preservative use are required to allow clinical interpretation of the data presented here.